PRODUCT ION OF THE CYTOKINES INTERLEUKIN-1 AND INTERLEUKIN-6 BY MURINE BRAIN MICROVESSEL ENDOTHELIUM AND SMOOTH-MUSCLE PERICYTES

PRODUCT ION OF THE CYTOKINES INTERLEUKIN-1 AND INTERLEUKIN-6 BY MURINE BRAIN MICROVESSEL ENDOTHELIUM AND SMOOTH-MUSCLE PERICYTES
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DOI:
10.1016/0165-5728(93)90281-3
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发表时间:
1993-08-01
影响因子:
3.3
通讯作者:
HART, MN
HART, MN
中科院分区:
医学4区
文献类型:
--
作者:
FABRY, Z;FITZSIMMONS, KM;HART, MN

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从新生的BALB/c(正常品系)和SJL/j(自身免疫易感品系)小鼠中培养小鼠脑微血管内皮细胞和平滑肌/周细胞(SM/P)细胞。评价这些细胞产生白细胞介素(IL)-1和IL-6细胞因子的能力。用IL-1 α、IL-1 β和IL-6特异性引物进行聚合酶链反应,在高度纯化的BALB/c内皮细胞和SM/P细胞中显示IL-1和IL-6的mRNA表达。在未刺激的SJL/j脑微血管细胞中检测到IL-6 mRNA,但未检测到IL-1 mRNA。原位杂交证实了IL-1和IL-6 mRNA在BALB/c脑微血管内皮细胞和SM/P中的存在。经DIO.G4.1测定,未受刺激的BALB/c内皮细胞产生活性IL-1的能力高于SM/P。经B 9生物测定,在内皮细胞和SM/P的上清液中检测到少量活性IL-6。IL-6的产生也显示出通过细胞的IL-1 β活化而上调。与BALB/c来源的内皮细胞相比,SJL/j来源的脑微血管内皮细胞释放等量的IL-6。而SJL/j来源的SM/P细胞IL-6的产生量明显高于BALB/c来源的SM/P细胞。这些观察结果,连同我们以前的数据表明,脑微血管SM/P细胞产生GM-CSF,强调脑微血管SM/P以及内皮细胞在中枢神经系统的炎症反应中的积极参与的可能性。
Murine brain microvessel endothelial cells and smooth muscle/pericytes (SM/P) cells were cultured from newborn BALB/c (normal strain) and SJL/j (autoimmune-prone strain) mice. These cells were evaluated for their ability to produce interleukin (IL)-1 and IL-6 cytokines. The expression of mRNA for IL-1 and IL-6 was shown in highly purified BALB/c endothelial cells and SM/P cells using polymerase chain reaction with specific primers for IL-1alpha, IL-1beta and IL-6. IL-6 but not IL-1 mRNA was detected in unstimulated SJL/j brain microvessel cells. The presence of IL-1 and IL-6 mRNA in the BALB/c brain microvessel endothelial cells and SM/P was confirmed by in situ hybridization. By DIO.G4.1 assay, unstimulated BALB/c endothelial cells were shown to produce active IL-1 to a higher degree than SM/P. By B9 bioassay, a low amount of active IL-6 was detected in the supernatant of endothelial cells and SM/P. The production of IL-1 and IL-6 in the bioassays was upregulated by lipopolysaccharide (LPS) activation of the cells in a time- and dose-dependent way. IL-6 production was also shown to be upregulated by IL-1beta activation of the cells. Brain microvessel endothelial cells of SJL/j origin released equivalent amounts of IL-6 compared to endothelial cells of BALB/c origin. However, the production of IL-6 was markedly higher in SM/P of SJL/j origin than in those of BALB/c origin. These observations, together with our previous data showing that brain microvessel SM/P cells produce GM-CSF, emphasize the possibility for active participation of brain microvasculature SM/P as well as endothelium in inflammatory reactions of the central nervous system.